Radiopharmaceuticals may be used as diagnostic or therapeutic agents by virtue of the physical properties of their constituent radionuclides. Thus, their utility is not based on any pharmacologic action. Most clinically used drugs of this class are diagnostic agents incorporating a gamma-emitting nuclide which, because of physical or metabolic properties of its coordinated ligands, localises in a specific organ after intravenous injection. The resultant images can reflect organ structure or function. These images are obtained by means of a gamma camera that detects the distribution of ionising radiation emitted by the radioactive molecules. The principal isotope currently used in clinical diagnostic nuclear medicine is metastable technetium-99m (t.sub.1/2 6 hrs).
The preparation of .sup.99m Tc radiopharmaceuticals generally requires addition of generator-produced Na.sup.99m TcO.sub.4 eluate to a ligand or ligands in the presence of a reducing agent. Many reducing agents have been used to this effect including tin metal, stannous ion, sodium borohydride, ferrous ascorbate, ferrous ion and formamidine sulphonic acid. These procedures often lead to Tc complexes containing Tc=O moiety, where the technetium is in the +4 or +5 oxidation state. The formation of such radiopharmaceutical complexes can often occur via substitution reactions on [Tc.sup.V OX.sub.5 ].sup.2- or [Tc.sup.IV X.sub.6 ].sup.2- molecules, which has been identified as a route of significant synthetic utility (Deutsch E, Libson K., Jurisson S., Lindoy L. F., Technetium Chemistry and Technetium Radiopharmaceuticals, Prog. Inorg. Chem (1982) 30 p 175). Only under harsh reaction conditions in the presence of powerful reducing agents and/or strong acids or bases are Tc.sup.I oxidation state complexes attained and stabilised. A limitation to the formation of novel radiopharmaceutical products is the tendency towards formation of Tc=O species, but in addition formation of Tc.sup.4+ or Tc.sup.5+ complexes also limits the number and/or type of ligands prone to bind to the metal.
PCT Application WO 85/03063 describes the synthesis of the TcN moiety as an intermediate in the preparation of radiopharmaceuticals by virtue of its ability to undergo various ligand substitution reactions. The TcN core is again primarily based on the +5 oxidation state of Tc.
The reaction of TcCl.sub.6.sup.2- with hydroxylamine salts under a variety of conditions to form a variety of complexes containing Tc-NO moiety have been described (Eakins, JCS (1963) 6012; Radonovich and Hoard, J Phys Chem, 88 (26) (1984) 6713; Armstrong and Taube, Inorg Chem (1976) 15 (3), 1904). This literature is concerned with .sup.99 Tc and not with its metastable isotope .sup.99m Tc. .sup.99 Tc has a half life of 2.1.times.10.sup.5 years, decays by emitting beta particles, and is of no interest as a radio-pharmaceutical.
M. W. Heitzmann et al (Journal of Labelled Compounds and Radiopharmaceuticals, Volume XVIII No. 4, (1981) 535-543) has described a method for reacting pertechnetate ion (TcO.sub.4.sup.-) with hydroxylamine hydrochloride in the presence or absence of a reducing agent, to yield paramagnetic .sup.99 Tc complexes.